Suzuki-Miyaura Cross-Coupling of 2-Pyridyl Trimethylammonium Salts by N-C Activation Catalyzed by Air- and Moisture-Stable Pd-NHC Precatalysts: Application to the Discovery of Agrochemicals

We report the first Suzuki-Miyaura cross-coupling of 2-pyridyl ammonium salts by highly selective N-C activation catalyzed by air-and moisture-stable Pd(II)-NHC (NHC = N- heterocyclic carbene) precatalysts. The use of well-defined and highly reactive [Pd(IPr)(3-CF3-An)Cl2] (An = aniline) or [Pd(IPr)(cin)Cl] (cin = cinnamyl) Pd(II)-NHC catalysts permits an exceptionally broad scope of the cross-coupling to furnish valuable biaryl and heterobiarylpyridines that are ubiquitous in medicinal chemistry and agrochemistry research. The overall process leverages the Chichibabin C-H amination of pyridines with N-C activation to enable an attractive strategy to the 2-pyridyl problem. The utility of the method to the discovery of potent agrochemicals is presented. Considering the importance of 2-pyridines and the versatility of N-C activation methods, we envision that this new C-H/N-C activation strategy will find broad application.

Automated summary

In this study, the first Suzuki-Miyaura cross-coupling of 2-pyridyl ammonium salts using air-and moisture-stable Pd(II)-NHC precatalysts was reported. The highly selective N-C activation reaction was catalyzed by [Pd(IPr)(3-CF3-An)Cl2] or [Pd(IPr)(cin)Cl] Pd(II)-NHC catalysts, resulting in the synthesis of valuable biaryl and heterobiarylpyridines. The utility of this method in the discovery of potent agrochemicals was also demonstrated.